OBJECTIVE - To study the role of the Gly(971)Arg variant of the insulin receptor substrate 1 (IRS-1) gene in the development of NIDDM in the Chinese population living in Taiwan. RESEARCH DESIGN AND METHODS - A total of 82 unrelated normal control subjects, 89 subjects with NIDDM, and 23 multiplex families were recruited in Taiwan. All of them were Han Chinese. Pedigree members without a history of diabetes were studied by the standard 75-g oral glucose tolerance test. Detection of the Gly(971)Arg variant of the IRS-1 gene was performed by polymerase chain reaction and restriction fragment-length polymorphism analysis. RESULTS - The frequency of Gly(971)Arg variant of the IRS-1 gene in the normal population was 1.2%, which was lower than frequencies reported in white populations. The prevalence of the Gly(971)Arg variant was not significantly increased in both the nonselected NIDDM population (1.1%) and the probands of the multiplex families (4.3%). More importantly, the Gly(971)Arg variant of the IRS-I gene did not cosegregate with BMI and NIDDM in these families. CONCLUSIONS - The Gly(971)Arg variant of the IRS-1 gene is an infrequent normal allele among Taiwanese. This variant is neither associated nor cosegregated with NIDDM in the Taiwanese population and families. Gly(971)Arg of IRS-1 gene does not play an important role in the development of NIDDM in this population.